Two Anticancer Drugs Target The Spliceosome

Scientists have identified the cellular target of two important anticancer molecules as a component of the spliceosome, according to two papers to be published in the September 2007 issue of Nature Chemical Biology.

The spliceosome is a large biological 'machine' that helps turn DNA into proteins. In particular, it binds to pre-mRNA (which is a direct copy of the DNA sequence) and cuts out the unnecessary nucleotides, resulting in mRNA that can then be converted into proteins. Until this point, no small molecules were known that could inhibit this process.

The two separate studies, led by Minoru Yoshida and Yoshiharu Mizui, were focused on finding out how two potent antitumor compounds actually work inside the cell. In both cases, the researchers now identify the cellular target of their compounds as SF3b, which is one portion of the spliceosome. These reports are important because they tell us that the spliceosome can be inhibited by small molecules, which highlights the potential of the splicesome as an anticancer target. By knowing the target of these molecules, scientists will be able to improve the design of anticancer compounds as well as create new potential drugs. In addition, the use of targeted compounds as 'chemical probes' will also allow researchers to learn more about the spliceosome, both in normal and cancerous cells.